African Horse Sickness (AHS) is a serious, often fatal, arthropod-borne viral disease of horses and mules (African Horse Sickness, The Merck Veterinary Manual). The mortality rate can be as high as 95% in some forms of this disease. Asymptomatic or mild infections can occur in horses, as well as zebras and donkeys, especially horses that were previously infected with a different serotype of the virus. Infected animals or vectors may carry the virus into AHS-free regions. Some authors speculate that climate change could increase the risk for spread of arthropod-borne diseases such as African Horse Sickness, as recently has occurred with related bluetongue virus (Wilson A et al., Parasitol. Res. 2008; 103:69-77). Culicoides imicola, the principal vector for this disease, has made incursions into North Africa and southern Europe. Potential arthropod vectors also exist throughout virtually all regions of the world, including much of the United States and the rest of the Americas.
African Horse Sickness results from infection with the African Horse Sickness Virus, a member of the genus Orbivirus in the family Reoviridae. To date, 9 serotypes of African Horse Sickness Virus are known. African Horse Sickness Virus serotype 9 is widespread in endemic regions, while serotypes 1 to 8 are found primarily in limited geographic areas. Serotype 9 has been responsible for the majority of African Horse Sickness outbreaks outside Africa. Serotype 4 caused one outbreak in Spain and Portugal between 1987 and 1990 (Lubroth J., Equine Pract. 1988; 10:26-33).
Initial research on African Horse Sickness Virus resulted in the development of mouse-brain attenuated modified live virus vaccine to African Horse Sickness Virus in the 1930's. These vaccines were refined and resulted in the development of a tissue culture attenuated modified live virus (MLV) vaccine in the 1960's.
Despite the efficacy of this vaccine, it has some inherent limitations including vaccine reactions (including death) in individual animals, varied immune response in individual animals, difficulty in immunizing young animals with passive maternal immunity, possibility of reversion to virulence of vaccine virus, and recombination of vaccine strains following vaccination with possible reversion to virulence (du Plessis M. et al. 1998, Onderstepoort Journal of Veterinary Research 65: 321-329). There are also socio-economic implications with using the MLV vaccine. South Africa has a protocol that allows it to export horses to the European Union and a number of other countries. This protocol also makes it possible for horses from other countries to enter South Africa to compete in various events or stand at stud for a temporary period. The protocol is based on ensuring that horses are adequately vaccinated against African Horse Sickness Virus. Veterinary Authorities are aware of the possible dangers of using the MLV vaccine. Most of these problems would be greatly reduced by the development of alternate African Horse Sickness Virus vaccines.
The African Horse Sickness Virus genome is composed of ten double-stranded RNA segments (Oellermann, R. A. et al., 1970; Bremer, C. W. et al., 1976), which encode at least ten viral proteins. The genome segments are numbered 1-10 in order of their migration in PAGE. Seven of the viral proteins are structural and form the double-shelled virus particle. The outer capsid is composed of two major viral proteins, VP2 and VP5, which determine the antigenic variability of the African Horse Sickness Viruses, while the inner capsid is comprised of two major (VP3 and VP7) and three minor (VP1, VP4 and VP6) viral proteins (Lewis S A and Grubman M J, 1991); Martinez-Torrecuadrada J L et al., 1994); Bremer, C W, et al. 1990; Grubman, M. J. & Lewis, S. A., 1992). VP3 and VP7 are highly conserved among the nine serotypes (Oellermann et al., 1970; Bremer et al., 1990). At least three non-structural proteins, NS1, NS2 and NS3, have been identified (Huismans, H. & Els, H. J., 1979); van Staden, V. & Huismans, H., 1991); Mizukoshi, N. et al., 1992).
Recombinant canarypox viruses derived from attenuated viruses have been developed as vectors for the expression of heterologous viral genes. A number of these canarypox constructs have since been licensed as vaccines in many countries, including South Africa, the European Union and the United States of America for use in horses (Minke J M, et al., 2004a and b; Minke J M, et al., 2007; Siger L, et al. 2006) and other species (Poulet H, et al., 2003).
The fact that these vaccines only contain genes of the organism of interest makes them inherently safe (Minke J M, et al., 2004b). Furthermore, the onset of detectable neutralizing antibody is rapid even after a single dose of vaccine (Minke J M et al., 2004b). The inherent safety of such vaccines and the nature of the development of neutralizing antibody make such vaccines particularly attractive for use in epizootics (Minke J M et al., 2004a).
Previous studies have shown that horses develop neutralizing antibodies to AHS when they are inoculated with exogenously expressed VP2 and an appropriate adjuvant (Scanlen M, et al., 2002). Studies in sheep have shown that the neutralizing antibody response to Bluetongue Virus is enhanced by inoculation of sheep with virus-like particles in which VP2 and VP5 are co-expressed (Pearson L D, Roy P, 1993). A recombinant canarypox virus vaccine co-expressing the genes encoding for VP2 and VP5 outer capsid proteins of Bluetongue Virus has recently been shown to induce high levels of protection in sheep (Boone J D, et al., 2007).
It has not been shown that horses develop neutralizing antibodies to African Horse Sickness Virus when inoculated with a vector containing and co-expressing AHSV VP2 and VP5. It can thus be appreciated that the present invention fulfills a need in the art by providing a recombinant poxvirus including compositions and products therefrom, particularly ALVAC-based recombinants and compositions and products therefrom, especially such recombinants expressing AHSV VPs 2 and 5 or any combination thereof and compositions and products therefrom.
Citation or identification of any document in this application does not constitute an admission that such document is available as prior art to the present invention.